This research will be done primary in Bolivia at the Proinpa Foundation in collaboration with Dr. Jean Greenberg, as an extension of NIH Grant R01 GM 054292. It is widely appreciated that bacterial pathogens can cause tremendous loss of human lives. Less appreciated, perhaps, is the importance of the relationship between bacterial pathogens, plants and human health. In the developing world, the human health begins from having an adequate supply of nutritious food, usually derived from plants. One of the most important crops in Andean countries (Bolivia, Peru and Ecuador) is the potato. Most of the small farmers of the highland areas depend on potato as their main daily source of food and income. In Bolivia, the potato crop is severely affected by bacterial wilt caused by Ralstonia solanacearum (Rs), one of the most aggressive pathogens that causes up to 90% losses in potato production. Currently, the only approach to control Rs is to promote agricultural practices that minimize the dispersal of bacteria from infected plants. Understanding the molecular basis of Rs-potato interaction will provide crucial tools for creating disease resistant potatoes. The pathogenicity of Rs lies mainly in the action of consortium of virulence proteins called effectors that the bacteria secrete via a specialized type III apparatus. These proteins can also act as avirulence (Avr) factors to induce defense responses that activate disease resistance in plants harboring the cognate resistance (R) genes. Three cases of Avr proteins from Rs have been documented (5;12;33). A common defense response to Avr proteins secreted by pathogens in plants is mediated by the specific action of R genes and leads to the production of an antimicrobial environment and localized programmed cell death. We are interested in identifying the Rs Avr cell death effectors that activate defense responses in potato and defining the possible plant defense molecules that interact with these effectors. In the long term, this project will expand the options available to plant breeders and give tools to engineer plants genetically to achieve more durable resistance. We previously made a large collection of effectors from a Bolivian Rs strain representative of the most aggressive Rs subgroups (Phylotype 2, Race 3, Biovar 2). A number of these effectors are sufficient to elicit cell death in a resistant, but inedible potato variety that could be used to find resistance traits that could be transferred to other edible varieties. Here, we propose to determine which cell death effectors have defense-inducing (Avr) properties. For the subset of bona fide Avr effectors, we will determine their subcellular localization in plants cells. Finally we will characterize the interactions of the Avr effectors with potential host target proteins. This work will have the added benefit of contributing to the control of phylotype 2 race 3 biovar 2 Rs strains, a group considered a bioterror threat in the USA. Public Health Relevance: Bacterial wilt caused by Ralstonia solanacearum affects potato, one of the most important crop of Bolivian agriculture. To create more durable and efficient resistant plants we will identify defense-response inducing effectors.